Unfolded Protein Response and A Possible Treatment for CFS

[Violeta]

I am not sure i am following you Violeta. Are you implying that the regimen could lead to cancer? Please elaborate your hypothesis so we can understand more.

I had been wondering about incorrectly folded proteins and where viruses, being proteins and being involved in the neurological diseases such as Alzheimer's and Parkinson's, fit in. Unfortunately, they are with you for life, unlike drugs or other metabolic disrupters.

I hope this explains it. I had insomnia last night and am not very verbal this morning.

http://www.ncbi.nlm.nih.gov/pubmed/17049016

http://www.ncbi.nlm.nih.gov/pubmed/8986292

So ebv would be one case in which hsp 70 unfortunately sustains the life of the infected cells. I don't think all viruses are like this. Taking arginine supposedly helps to deal with the ebv, even when it's not in cancerous tumors, but that can reactivate herpes simplex. It's a difficult situation.

 

[mariovitali]

@Violeta,

Have you tried the regimen which is dicussed in this Thread?

 

[Hip]

@mariovitali
Do you know if ursodeoxycholic acid (UDCA) can be used instead of tauroursodeoxycholic acid (TUDCA) for the purpose of mitigating protein misfolding and endoplasmic reticulum stress? Both are bile acids.

The reason I ask is because a while ago I was looking at taking UDCA, as it theoretically I think it may help fight the intracellular viral infections associated with ME/CFS (UDCA induces cathelicidin in the cell, 1 which then enables TLR3 to respond to viral dsRNA).

So if UDCA also helps prevent protein misfolding, I could use that, and then kill two birds with one stone.

 

[mariovitali]

@Hip

It should be ok :

Lipids and detergents (bile acids)
Bile acids (BAs) are acidic steroids that are synthesized from cholesterol in the liver. They are secreted into the intestine where they can be dehydroxylated by bacteria to become secondary BAs like deoxycholic acid (DCA) or ursodeoxycholic acid (UDCA). Secondary BAs can then be returned to the liver and conjugated with amino acids to generate conjugated BAs such as tauroursodeoxycholic acid (TUDCA) which is UDCA conjugated with the amino acid taurine. BAs are the major constituents of bile. While their main role is the solubilization of dietary fats and fat-soluble vitamins to improve absorption from the intestinal lumen, in recent years, neuroprotective functions have been attributed to BAs.44,45



Mechanisms of action
TUDCA and UDCA can reduce the accumulation of toxic aggregates in different experimental models of neurodegenerative diseases. As such, they have been classified as chemical chaperones. However, as is the case for PBA, the observed treatment benefits may also be the result of other functions attributed to these bile acids.46

The cytoprotective effects of UDCA and TUDCA have been attributed to the reduction of reactive oxygen species formation,47 the prevention of mitochondrial dysfunction,48 and the inhibition of apoptosis through both the intrinsic49 and the extrinsic pathway.50

These steroids can also activate specific nuclear receptors and G protein–coupled receptors influencing the expression of genes that encode proteins involved in the regulation of glucose, fatty acid, lipoprotein synthesis, energy metabolism, and the regulation of their own synthesis.51

EDIT: (Thank you @Ema) :

As our life expectancy and population numbers continue to increase, so will the prevalence and socioeconomic burden of neurodegenerative diseases. Given this, it is of some urgency to find viable therapeutic strategies. Since the accumulation of misfolded host proteins in the brain is the putative cause for many of these diseases, stabilizing native protein structure is a logical approach. TUDCA and UDCA, which can have anti-aggregation effects as well as effects on apoptosis regulation, may represent safe and effective compounds which act at more than one level of the neuropathogenic cascade. More studies with these promising compounds should be pursued to fully understand their mechanism(s) of action and to expand the repertoire of treatable neurodegenerative diseases.

Link :

The therapeutic potential of chemical chaperones in protein folding diseases

 

[Ema]

http://www.gahmj.com/doi/abs/10.7453/gahmj.2014.017

This says that they both stabilize protein folding.

 

[JPV]

Do you know if ursodeoxycholic acid (UDCA) can be used instead of tauroursodeoxycholic acid (TUDCA) for the purpose of mitigating protein misfolding and endoplasmic reticulum stress? Both are bile acids.

It seems a lot cheaper too except I'm only seeing it being sold for pets in the US and as a pharmaceutic in Europe. What sources are you finding?

 

[Hip]

@mariovitali
I should add that several of the supplements you are taking are cathelicidin inducers: curcumin, resveratrol and vitamin D3 all induce cathelicidin.

I am not sure if this is a coincidence. Incidentally, the Marshall Protocol, which is sometimes used to treat ME/CFS, also works by inducing this intracellular antimicrobial peptide cathelicidin (via the VDR agonist drug Benicar).

I am wondering whether TUDCA might also induce cathelicidin, as well as UDCA. But I could not find any info on this.

It seems a lot cheaper too except I'm only seeing it being sold for pets in the US and as a pharmaceutic in Europe. What sources are you finding?

I had not actually searched for a source of UDCA before, but I notice it's sold at Inhouse Pharmacy (see here: Ursodeoxycholic Acid) at $2 per 300 mg pill, which seems pretty expensive. That's $6.70 a gram. Though International Drug Mart sell it cheaper for $1.50 per 300 mg pill.

Are you sure you are finding UDCA cheaper than TUDCA?

TUDCA powder I found here costing $40 for 25 grams, so that's $1.60 a gram.

Were the pet supply sources of UDCA cheaper than the pharmaceutical UDCA sources?

 

[JPV]

Are you sure you are finding UDCA cheaper than TUDCA?

TUDCA powder I found here costing $40 for 25 grams, so that's $1.60 a gram.

Were the pet supply sources of UDCA cheaper than the pharmaceutical UDCA sources?

I thought the price I saw was per bottle. Now that I'm looking at it closer it was per tablet.

$2.68 USD per 250mg tablet. So no... it's not cheaper.

 

[mariovitali]

@Hip

I just looked at the PubMed entries about cathelicidin , TUDCA has no hits but UPR has :

*********Topic : cathelicidin ***************
vitamin_d3.csv : 0.31 %
mast_cell_activation.csv : 0.16 %
scfa.csv : 0.14 %
immune_response.csv : 0.12 %
mcp-1.csv : 0.07 %
butyrate.csv : 0.07 %
microbiome_humans.csv : 0.06 %
inflammatory_response.csv : 0.06 %
rxr.csv : 0.06 %
upr.csv : 0.06 %
hmgb1.csv : 0.06 %
er_stress.csv : 0.05 %
accutane.csv : 0.05 %
caspase_human.csv : 0.04 %
protease_inhibitor.csv : 0.04 %
pbmc.csv : 0.04 %
coenzymeq10.csv : 0.04 %
histone_deacetylase.csv : 0.03 %
calcium_homeostasis.csv : 0.03 %
crohns_disease.csv : 0.03 %
stat1.csv : 0.03 %
nadph_human.csv : 0.03 %
curcumin.csv : 0.03 %
resveratrol.csv : 0.03 %
ros.csv : 0.03 %
il_10.csv : 0.02 %
microglia.csv : 0.02 %
phospholipid_human.csv : 0.02 %
sinusitis.csv : 0.02 %
inducible_nos.csv : 0.02 %
advanced_glycation_end.csv : 0.02 %
cyp3a4.csv : 0.02 %
udpgluc.csv : 0.02 %
cfs.csv : 0.02 %
p450oxidoreductase.csv : 0.01 %
glycoproteins.csv : 0.01 %
glycosylation.csv : 0.01 %
n-acetylglucosamine.csv : 0.01 %
probiotics.csv : 0.01 %
phosphatidylcholine.csv : 0.01 %
ckd.csv : 0.01 %
rituximab.csv : 0.01 %
heat_shock_protein.csv : 0.01 %
oxidative_stress_markers.csv : 0.01 %
p53.csv : 0.01 %
hsp70.csv : 0.01 %
human_semen.csv : 0.01 %
chaperones.csv : 0.00 %
cortisol_levels.csv : 0.00 %
autism.csv : 0.00 %
l-arginine.csv : 0.00 %
amyloid.csv : 0.00 %
glutamate.csv : 0.00 %
ngf.csv : 0.00 %
hepatocytes.csv : 0.00 %
inositol.csv : 0.00 %
insulin_resistance.csv : 0.00 %
cholestasis.csv : 0.00 %
tudca.csv : 0.00 %
choline_deficiency.csv : 0.00 %
dolichol.csv : 0.00 %
insomnia.csv : 0.00 %
5-htp.csv : 0.00 %
adrenal_hyperplasia.csv : 0.00 %
omega3.csv : 0.00 %
mastocytosis.csv : 0.00 %
vitamin_k2.csv : 0.00 %
p450scc.csv : 0.00 %
limbic_system.csv : 0.00 %
dopamine.csv : 0.00 %
sirt1.csv : 0.00 %
5mthf.csv : 0.00 %
panic_disorder.csv : 0.00 %
neuronal_nos.csv : 0.00 %
adhd.csv : 0.00 %
iron_deficiency.csv : 0.00 %
dpagt1.csv : 0.00 %
pgc1.csv : 0.00 %
dht.csv : 0.00 %
phenylketonuria.csv : 0.00 %
irritable_bowel.csv : 0.00 %
sshl.csv : 0.00 %
steatohepatitis.csv : 0.00 %
5alphareductase.csv : 0.00 %
l_tyrosine.csv : 0.00 %
ire1.csv : 0.00 %
nafld.csv : 0.00 %
gtp_cyclohydrolase.csv : 0.00 %
ebv.csv : 0.00 %
misfolded_proteins.csv : 0.00 %
3betahsd.csv : 0.00 %
nlinkedglycosylation.csv : 0.00 %
endothelial_nos.csv : 0.00 %
hmgcoa.csv : 0.00 %
gaba_human.csv : 0.00 %
gpr78.csv : 0.00 %
urea_cycle.csv : 0.00 %
xbp1.csv : 0.00 %
orthostatic_intolerance.csv : 0.00 %
cerebrovascular_amyloidosis.csv : 0.00 %
social_anxiety.csv : 0.00 %
systemic_amyloidosis.csv : 0.00 %
oxalates.csv : 0.00 %
udpglcnac.csv : 0.00 %
adrenal_insufficiency.csv : 0.00 %
perk.csv : 0.00 %
peroxynitrite.csv : 0.00 %
hydroxysteroid_dehydrogenase.csv : 0.00 %
finasteride.csv : 0.00 %
hexosamine.csv : 0.00 %
adrenergic_receptor.csv : 0.00 %
selenium_deficiency.csv : 0.00 %
glycerylphosphorylcholine.csv : 0.00 %
gluten.csv : 0.00 %
benfotiamine.csv : 0.00 %
vcam-1.csv : 0.00 %
cimetidine.csv : 0.00 %
anhedonia.csv : 0.00 %
tocotrienol.csv : 0.00 %
human_proteinuria.csv : 0.00 %
cyp2d6.csv : 0.00 %
fmo3.csv : 0.00 %
dopamine_levels.csv : 0.00 %
baroreceptor.csv : 0.00 %
rar.csv : 0.00 %
neurite_outgrowth.csv : 0.00 %
mitochondrial_dysfunction.csv : 0.00 %
p5p.csv : 0.00 %
pqq.csv : 0.00 %
cyp1a2.csv : 0.00 %
beta-alanine.csv : 0.00 %
testosterone_production.csv : 0.00 %
freet3.csv : 0.00 %
car.csv : 0.00 %
uric_acid.csv : 0.00 %
mucuna.csv : 0.00 %
vitamin_b6.csv : 0.00 %
hepatotoxicity.csv : 0.00 %
dysautonomia.csv : 0.00 %
nadh_human.csv : 0.00 %
ginkgo.csv : 0.00 %
caloric_restriction.csv : 0.00 %
lipoic_acid.csv : 0.00 %
allopregnanolone.csv : 0.00 %
monosodium_glutamate.csv : 0.00 %
tetrahydrobiopterin.csv : 0.00 %
mthfr.csv : 0.00 %
taurine.csv : 0.00 %
amyloidosis.csv : 0.00 %
steroidogenesis_human.csv : 0.00 %
l_tryptophan.csv : 0.00 %
creatine_supplementation.csv : 0.00 %
cyp1b1.csv : 0.00 %
serotonin_levels.csv : 0.00 %
dihydroprogesterone.csv : 0.00 %
cyp2e1.csv : 0.00 %
cyp1a1.csv : 0.00 %
selenium.csv : 0.00 %
hsc.csv : 0.00 %
osmolytes.csv : 0.00 %
floaters.csv : 0.00 %
acetyl-coa.csv : 0.00 %
pregnenolone.csv : 0.00 %
acetylcholine.csv : 0.00 %
asymmetric_dimethylarginine.csv : 0.00 %
triiodothyronine_levels.csv : 0.00 %
d-limonene.csv : 0.00 %
resistant_starch.csv : 0.00 %
trpv.csv : 0.00 %
l-dopa.csv : 0.00 %
tinnitus.csv : 0.00 %
zinc_supplementation.csv : 0.00 %
excitotoxicity.csv : 0.00 %
hpa_axis.csv : 0.00 %
tau.csv : 0.00 %
hgh.csv : 0.00 %
tmao.csv : 0.00 %
atrial_fibrillation.csv : 0.00 %
magnesium_deficiency.csv : 0.00 %
subclinicalhypo.csv : 0.00 %
o-glcnac.csv : 0.00 %
star.csv : 0.00 %
l_carnitine.csv : 0.00 %
srd5a3.csv : 0.00 %
oxidative_stress_protection.csv : 0.00 %
pxr.csv : 0.00 %

 

[mariovitali]

@Hip

Endoplasmic reticulum stress: key promoter of rosacea pathogenesis.

Recent scientific interest in the pathogenesis of rosacea focuses on abnormally high facial skin levels of cathelicidin and the trypsin-like serine protease kallikrein 5 (KLK5) that cleaves the cathelicidin precursor protein into the bioactive fragment LL-37, which exerts crucial proinflammatory, angiogenic and antimicrobial activities. Furthermore, increased expression of toll-like receptor 2 (TLR2) has been identified in rosacea skin supporting the participation of the innate immune system. Notably, TLRs are expressed on sensory neurons and increase neuronal excitability linking TLR signalling to the transmission of neuroinflammatory responses. It is the intention of this viewpoint to present a unifying concept that links all known clinical trigger factors of rosacea such as UV irradiation, heat, skin irritants and special foods to one converging point: enhanced endoplasmic reticulum (ER) stress that activates the unfolded protein response (UPR). ER stress via upregulation of transcription factor ATF4 increases TLR2 expression, resulting in enhanced production of cathelicidin and KLK5 mediating downstream proinflammatory, angiogenic and antimicrobial signalling. The presented concept identifies rosacea trigger factors as environmental stressors that enhance the skin's ER stress response. Exaggerated cutaneous ER stress that stimulates the TLR2-driven inflammatory response may involve sebocytes, keratinocytes, monocyte-macrophages and sensory cutaneous neurons. Finally, all antirosacea drugs are proposed to attenuate the ER stress signalling cascade at some point. Overstimulated ER stress signalling may have evolutionarily evolved as a compensatory mechanism to balance impaired vitamin D-driven LL-37-mediated antimicrobial defenses due to lower exposure of UV-B irradiation of the northern Celtic population.

So cathelicidin levels are increased after ER Stress takes place.

 

[Violeta]

@Violeta,

Have you tried the regimen which is dicussed in this Thread?

The supplements that I take that I have in common with you are choline, taurine, selenium, Vitamin C, and B12. I also eat low protein, and although your protocol doesn't emphasize low purine, that is how I chose to do it.

Have you looked into the replication of viruses through heat shock proteins? The very things that you recommend people with ME/CFS to avoid are the things that might be the most helpful.

Is it possible that that part of your condition needs to be addressed differently than someone with ME/CFS?

It's no secret that EBV infection often precedes cancer.

 

[Hip]

So cathelicidin levels are increased after ER Stress takes place.

Might that mean that by reducing ER stress, cathelicidin induction might be less, or is it more complicated than that? Perhaps it depends on how you reduce ER stress, since curcumin, resveratrol and vitamin D3 all induce cathelicidin.

 

[mariovitali]

@Violeta

Have you looked into the replication of viruses through heat shock proteins? The very things that you recommend people with ME/CFS to avoid are the things that might be the most helpful.

Which things specifically?

Is it possible that that part of your condition needs to be addressed differently than someone with ME/CFS?
It's no secret that EBV infection often precedes cancer.

Yes it could be possible and unfortunately i am not in any position to know what consequences the regimen i follow will have to me or to other people who choose to follow it.

 

[mariovitali]

Might that mean that by reducing ER stress, cathelicidin induction might be less, or is it more complicated than that? Perhaps it depends on how you reduce ER stress, since curcumin, resveratrol and vitamin D3 all induce cathelicidin.

All of these theories are possible. It would be great if we could have Biochemistry experts to answer these questions although it seems that a lot of things regarding ER Stress have yet to be discovered.

 

[mariovitali]

All,


One question : Do you have any CFS Symptoms whenever you are sick? I had none whenever i had a viral infection.

 

[mariovitali]

@Hip

This is a description on how the software works (actually there is more than one of them). Take a deep breath!


The first one is a Python library that connects to PubMed and submits Queries to abstracts. It then downloads all abstracts to a csv file.

The second software matches several topics of interest to the csv files that have been downloaded from PubMed.

At the moment of writing These topics are :

research_subj=["hmgb1"," p53 "," stat1 "," inositol ","adrenergic receptor","caloric restriction","hepatocyte","baroreceptor"," microglia ","immune response","irritable bowel","chaperone"," hepatic stellate cell "," tgfb1 "," perk ","xbp1","ire1","il-10","protease inhibitor","interferon","mcp-1","vcam-1","cimetidine","cholestasis","anhedonia","interleukin","glycerylphosphorylcholine","selenocysteine"," l-arginine ","vitamin k2"," tyrosine kinase ","beta-alanine","trpv","histone deacetylase"," nitroglycerin ","limbic","insomnia","dysautonomia","dexamethasone","reactive oxygen species","rituximab"," tau ","udp-glcnac"," b6 "," dopamine "," gaba ","mucuna"," enos "," inos "," nnos ","fmo3","5-htp"," oxalate ","human growth hormone"," iron ","autism","adhd","osmolyte","manganese","calcium","magnesium","phosphatidylcholine","asymmetric dimethylarginine"," trimethylamine ","trimethylamine-n-oxide","phospholipid","mitochondrial dysfunction","visceral fat","nafld","acetyl-coa","choline acetyltransferase"," acetylcholine ","advanced glycation end","benfotiamine"," hpa axis ","glycoprotein","mpdu1","dpagt1","hyperlipidemia","o-glcnac","n-acetylglucosamine","hexosamine"," glucosamine ","srd5a3","selenoprotein","probiotic","finasteride","accutane"," bile ","cyp1b1","cyp2d6","floaters","social anxiety","d-limonene","cholecalciferol","pyrroloquinoline","mk-4","grapefruit","nigella","omega","curcumin","lipoic","alcar","carnitine","ashwagandha","resveratrol","omega","zinc","magnesium","manganese","butyric","butyrate","l-tyrosine","5-mthf","gpx1","gpx2","gpx3"," nos1 "," nos2 "," nos3 ","tyrosine hydroxylase","tinnitus","cardiovascular"," choline ","homocysteine","uric acid"," semen ","hypothyroid","mastocytosis","mast cell","mastocytosis","histamine","triiodothyronine","dopamine","nrf-2","serotonin","adrenaline","noradrenaline","epinephrine","monoamine oxidase","estrogen","nerve growth factor","cyp2d6","proteinuria"," ammonia " ,"nitric oxide","phenylalanine","sinusitis","nrf1","nrf2","arrhythmia","pgc-1"," creb ","modafinil","methylphenidate","piracetam"," tyrosine ","sirt3","melatonin"," tryptophan ","ritalin"," mtor ","chronic kidney","glutathione","cancer","nitric oxide","n-linked","acetylcholinesterase","piracetam","scfa","anxiety disorder","cortisol"," amyloid precursor protein ","gsk-3","beta-amyloid"," ttr ","neurodegenerati"," gut ","steatohepatitis","microbiome","acetylated histone","ischemic reperfusion","acetylated histone","mnsod","cuznsod","sod1","sod2","sod3","sod4","hypocortisolism","hypercortisolism"," mrna ","butyrate","calcitonin","tauopath","insulin resistance","sinusitis","personality","hydroxysteroid dehydrogenase","alzheimer","parkinson","hsf-1","cortisol","catecholamine","intestina","insulin","hypoxia","ankyrin","80-kda","ribonuclease","pbmc","37-kda","restless","ugt1a1","immune","caspase","dermatitis","gpr78","glutathione","glucose","apoptosis","diabetes","mitochondri","inflammat","gch1","hepatic","constipat","ca2","liver","lymph","cyp1","cyp2","cyp3","p450","dysautonomia","glutam","cd20","dolichol","interstitial","magnesium","lymph","orthostatic","hyperviscosity","neurologic","depression","autonomic","hsp90","er stress","calcium homeostasis","caspase","aplp1","gelsolin","amyloidosis","p53","retinoic","calcium","dihydroprogesterone","allopregnanolone","androstane","pregnane","dehydrotestosterone","gluten","celiac","neuphropathy","prostate","platelet aggregation","hmg-coa","vitamin d3","ascorbic acid","nitric oxide","cytochrome","oxidative stress","testosterone","mthfr","methylation","peroxynitrite","thyroid","misfolded proteins","unfolded protein response","endoplasmic reticulum","selenium","magnesium","taurine","tudca","resveratrol","hsp70","dht","glycosylation","tetrahydrobiopterin","pregnenolone","progesterone","steroidogenesis","phenylketonuria","estradiol","shbg","free testosterone","hypogonadism","adrenal insufficiency","adrenal hyperplasia","igf1","sirt1"]


The csv files that have been downloaded are for the following PubMed entries :


tetrahydrobiopterin
nitric oxide
phenylalanine
tyrosine
phenylketonuria
dopamine
l-arginine
enos
tyrosine hydroxylase
liver
oxidative stress
dopamine
serotonin
mrna
inflammat
catecholamine
reactive oxygen species
inos
cardiovascular
tryptophan
neurologic
parkinson
diabetes
interferon
calcium
nnos
peroxynitrite
acetylcholine
iron
omega
cytochrome
immune
interleukin
glucose
glutathione
epinephrine
ca2
hepatic
gch1
depression
insulin
mitochondri
apoptosis
lymph
l-tyrosine
glutam
p450
neurodegenerati
adrenaline
ascorbic acid
noradrenaline
zinc
hepatocyte
homocysteine
cancer
intestina
dexamethasone
insulin resistance
chaperone
hypoxia
alzheimer
estrogen
asymmetric dimethylarginine
immune response
5-htp
autism
estradiol
melatonin
nitroglycerin
uric acid
manganese
nerve growth factor
hsp90
nos3
monoamine oxidase
magnesium
thyroid
platelet aggregation
caspase
nos2
autonomic
mitochondrial dysfunction
p53
phospholipid
microglia
resveratrol
hmg-coa
5-mthf
methylation
ammonia
carnitine
arrhythmia
nos1
hyperlipidemia
il-10
glycosylation
mast cell
hsp70
cortisol
proteinuria
endoplasmic reticulum
p53
vcam-1
nrf2
tau
butyric
selenium
glycoprotein
calcium homeostasis
tyrosine kinase
glucosamine
mcp-1
interstitial
b6
personality
advanced glycation end
beta-amyloid
gut
sod1
restless
retinoic
testosterone
choline
stat1
adhd
n-linked
hexosamine
creb
mthfr
hypothyroid
progesterone
sod3
acetylcholinesterase
gaba
adrenergic receptor
mucuna
phosphatidylcholine
cuznsod
histamine
histone deacetylase
n-acetylglucosamine
hydroxysteroid dehydrogenase
protease inhibitor
gpx1
choline acetyltransferase
sirt1
limbic
dht
chronic kidney
pbmc
triiodothyronine
dermatitis
ischemic reperfusion
modafinil
misfolded proteins
sod2
er stress
mtor
inositol
selenocysteine
steroidogenesis
piracetam
acetyl-coa
taurine
bile
lipoic
baroreceptor
ankyrin
celiac
calcitonin
caloric restriction
methylphenidate
vitamin d3
amyloidosis
glycerylphosphorylcholine
udp-glcnac
tgfb1
dysautonomia
tudca
80-kda
allopregnanolone
fmo3
dehydrotestosterone
cholestasis
ttr
finasteride
adrenal hyperplasia
cd20
tinnitus
vitamin k2
insomnia
trimethylamine-n-oxide
alcar
steatohepatitis
gluten
oxalate
mk-4
probiotic
semen
pregnane
scfa
visceral fat
butyrate
irritable bowel
hsf-1
anxiety disorder
floaters
nafld
pregnenolone
tauopath
dihydroprogesterone
cholecalciferol
beta-alanine
dpagt1
osmolyte
trimethylamine
ribonuclease
constipat
gelsolin
sod4
aplp1
hpa axis
mastocytosis
cyp2d6
orthostatic
nigella
grapefruit
srd5a3
social anxiety
mnsod
benfotiamine
pyrroloquinoline
microbiome
rituximab
neuphropathy
gsk-3
37-kda
amyloid precursor protein
nrf1
hypogonadism
d-limonene
gpr78
ashwagandha
dolichol
xbp1
sirt3
hmgb1
ire1
anhedonia
cimetidine
curcumin
trpv
o-glcnac
prostate
cyp1b1
androstane
accutane
hyperviscosity
ugt1a1
sinusitis
acetylated histone
hypocortisolism
hypercortisolism
human growth hormone
perk
free testosterone
hepatic stellate cell
nrf-2
adrenal insufficiency
igf1
mpdu1
ritalin
pgc-1
gpx3
shbg
unfolded protein response
gpx2
selenoprotein
cyp1
cyp2
cyp3


What the software does is to identify the frequency of each Topic within each csv. So for example the Topic TUDCA has the following matches to the csv files :

*********Topic : tudca ***************
tudca.csv : 49.53 %
xbp1.csv : 1.24 %
taurine.csv : 1.15 %
gpr78.csv : 0.95 %
er_stress.csv : 0.83 %
perk.csv : 0.59 %
upr.csv : 0.58 %
ire1.csv : 0.55 %
chaperones.csv : 0.22 %
misfolded_proteins.csv : 0.11 %
cholestasis.csv : 0.11 %
tmao.csv : 0.10 %
systemic_amyloidosis.csv : 0.07 %
hepatocytes.csv : 0.07 %
nafld.csv : 0.06 %
osmolytes.csv : 0.06 %
mitochondrial_dysfunction.csv : 0.04 %
oxidative_stress_markers.csv : 0.04 %
choline_deficiency.csv : 0.04 %
heat_shock_protein.csv : 0.04 %
advanced_glycation_end.csv : 0.03 %
caspase_human.csv : 0.03 %
butyrate.csv : 0.03 %
amyloid.csv : 0.03 %
amyloidosis.csv : 0.02 %
lipoic_acid.csv : 0.02 %
3betahsd.csv : 0.02 %
hmgcoa.csv : 0.02 %
cyp2e1.csv : 0.02 %
hepatotoxicity.csv : 0.02 %
cyp1a2.csv : 0.02 %
inositol.csv : 0.02 %
ros.csv : 0.02 %
excitotoxicity.csv : 0.02 %
dht.csv : 0.02 %
mcp-1.csv : 0.02 %
hydroxysteroid_dehydrogenase.csv : 0.02 %
microglia.csv : 0.01 %
vcam-1.csv : 0.01 %
monosodium_glutamate.csv : 0.01 %
endothelial_nos.csv : 0.01 %
glycosylation.csv : 0.01 %
oxidative_stress_protection.csv : 0.01 %
phosphatidylcholine.csv : 0.01 %
calcium_homeostasis.csv : 0.01 %
p53.csv : 0.01 %
tau.csv : 0.01 %
acetyl-coa.csv : 0.01 %
steatohepatitis.csv : 0.01 %
histone_deacetylase.csv : 0.01 %
uric_acid.csv : 0.01 %
human_proteinuria.csv : 0.01 %
hsp70.csv : 0.01 %
...
...
..

The software also outputs the matchings that are above a cutoff value :



After all topics are searched, we get the following csv file that contains all matchings on CSV files for all topics.

Then we can find the Linear correlation for any given topic with other Topics :

Finally we can execute Association Rule Mining as follows. I use a cutoff value after which a 'T' value is inserted, otherwise a 'F' value is inserted.

This is a snapshot for a cutoff of 0.5. Notice how on Row 3 we have T (=TRUE) values for acetylcholine and the adrenergic receptor. This means that for a Topic searched, these two csv files (acetylcholine.csv and adrenergic_receptor.csv) have matched with a frequency of more than 0.5 %

Next, we run the associations discovery for -say- er stress. If we have a high cutoff value then the results will be more or less known :


[upr=T] 76 == [er_stress=T] 75 conf (0.99) lift 3.45) lev 0.18) conv (27.14)
[gpr78=T] 74 == [er_stress=T] 71 conf (0.96) lift (3.36) lev (0.17) conv (13.21)
[ire1=T] 76 == [er_stress=T] 71 conf (0.93) lift (3.27) lev (0.16) conv (9.05)




So upr.csv and er_stress.csv are frequently matched to a given topic (say TUDCA) with a frequency value of -say- 1%. If we lower the cutoff value to 0.3% we get the following :


[p53=T, mitochondrial_dysfunction=T] 113 == [er_stress=T] 113 conf (1) lift (1.68) lev (0.15) conv (45.8)
[p53=T, peroxynitrite=T] 109 == [er_stress=T] 109 conf (1) lift (1.68) lev (0.15) conv (44.18)
[p53=T, tau=T] 108 == [er_stress=T] 108 conf (1) lift (1.68) lev (0.15) conv (43.77)
[ire1=T] 134 == [er_stress=T] 129 conf (0.96) lift (1.62) lev (0.16) conv (9.05)
[upr=T] 162 == [er_stress=T] 155 conf (0.96) lift (1.61) lev (0.19) conv (8.21)
[p53=T] 125 == [er_stress=T] 116 conf (0.93) lift (1.56) lev (0.14) conv (5.07)




We also have the File Matchings which i will discuss when i come back from Holidays

 

[Gondwanaland]

All,


One question : Do you have any CFS Symptoms whenever you are sick? I had none whenever i had a viral infection.

There has been such a discussion here at the boards before and many people reported the same as you.

 

[Violeta]

All,


One question : Do you have any CFS Symptoms whenever you are sick? I had none whenever i had a viral infection.

That's a tricky question. Do you mean you felt sick but weren't tired when you were sick?

Do you know which viral infections you had?

 

[mariovitali]

That's a tricky question. Do you mean you felt sick but weren't tired when you were sick?

Do you know which viral infections you had?

I mean symptoms such as tinnitus, orthostatic intolerance, brain fog, etc.

I had none of these symptoms whenever had a typical viral infection (which had symptoms of fever, throat pain, stuffed nose, cough etc)

 

[Violeta]

I mean symptoms such as tinnitus, orthostatic intolerance, brain fog, etc.

I had none of these symptoms whenever had a typical viral infection (which had symptoms of fever, throat pain, stuffed nose, cough etc)

How often have you had those viral symptoms, and did you have those viral symptoms previous to taking finasteride?